The majority of oocytes within the adult female ovary are enveloped and surrounded by follicular somatic cells (such as granulosa, theca and cumulus cells). During the early stages of development, the surrounded oocytes are maintained in a prolonged stage of first meiotic prophase. The growth and maturation of mammalian follicle cells and oocytes are dependent upon and intricately controlled by hormones, including gonadotropins, such as follicle stimulating hormone (FSH) and luteinizing hormone (LH) secreted by the anterior pituitary, and other local paracrine factors secreted by the surrounding follicular somatic cells.
Periodically, a group of primordial follicles enters a stage of follicular growth. During this time, the oocyte undergoes a large increase in volume and the number of surrounding follicular granulosa cells increases. In early stages of the cycle, maturing follicles respond to FSH with further growth and cellular proliferation. In later stages, FSH induces the formation of LH receptors on the granulosa cells. In response to LH, the first oocyte meiotic block is removed and the granulosa and theca cells of the ovaries begin to produce EGF-like factors and insulin-like 3. In response to these factors, the nuclear membranes of competent oocytes are then broken down (germinal vesicle nuclear envelope breakdown), the chromosomes assemble to undergo the first meiotic division and the first polar body is extruded in preparation of the oocyte for fertilization.
Because LH acts exclusively on somatic cells in the ovaries (e.g., granulosa and theca cells), local paracrine factors are involved in the regulation of oocyte meiosis arrest and optimal oocyte maturation. Therefore, in addition to the pituitary hormones FSH and LH, other factors are involved in the maturation process. For instance, the maturing oocyte synthesizes paracrine factors that allow the follicle cells to proliferate; while the follicle cells secrete growth and differentiation factors (for example TGF-β2, VEGF, EGF, leptin, and FGF2) that enhance angiogenesis and allow the oocyte to grow and mature. Another factor secreted by follicular somatic cells is brain-derived nuerotrophic factor (BDNF).
Because of the importance of oocyte maturation and preimplantation embryo development, there is a strong interest in developing novel compositions that are clinically useful for enhancing oocyte maturation and promoting pre-implantation embryo growth. Accordingly, the present invention is of great clinical interest because it provides novel BDNF containing compositions that are useful for the modulation of oocyte, zygote and preimplantation embryo development.